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New Study Evaluating the ADHD Medication VYVANSE(R) (lisdexamfetamine dimesylate) CII Demonstrated No Change in the Pharmacokinetic Profile of VYVANSE When Coadministered with Prilosec OTC(R) 40 mg (20 mg X 2), a Commonly Used Proton Pump Inhibitor (PPI)

May 22, 2009

PHILADELPHIA, May 22 /PRNewswire-FirstCall/ – Shire plc (LSE: SHP, Nasdaq: SHPGY), the global specialty biopharmaceutical company, announced results of a study showing that coadministration of the ADHD medication VYVANSE(R) (lisdexamfetamine dimesylate) CII with the proton pump inhibitor (PPI) Prilosec OTC(R) 40 mg (20 mg X 2), did not alter the median time it took for maximum plasma concentration of d-amphetamine to be reached in the subjects evaluated. In the same study, coadministration of Prilosec OTC with ADDERALL XR resulted in a nearly 45 percent reduction in the median time to reach maximum plasma concentrations of amphetamine, the active medication. Other pharmacokinetic parameters (maximum plasma concentration and area under curve) of active medication were not altered for either VYVANSE or ADDERALL XR when coadministered with Prilosec OTC. This study, which is the first to evaluate the pharmacokinetics of VYVANSE and ADDERALL XR taken alone and with Prilosec OTC 40 mg, was recently presented at the International Congress on Clinical Pharmacy, co-sponsored by the American College of Clinical Pharmacy (ACCP), in Orlando, FL.

“Since its approval for ADHD in adults in 2008, VYVANSE has been an important treatment option for physicians treating adult patients seeking significant ADHD symptom control during their busy day,” said Jeffrey Jonas, Senior Vice President of Research & Development for the Specialty Pharmaceuticals business at Shire. “This study is the first to evaluate the impact of a proton pump inhibitor on the amphetamine pharmacokinetics of VYVANSE and ADDERALL XR and further supports that, as a prodrug, VYVANSE does not rely on pH for its absorption or conversion.”

Heartburn is a common problem affecting millions of Americans. Prilosec OTC and other proton pump inhibitors reduce the acidity (increase the pH) in the stomach and are commonly used by millions of adults in the United States who suffer from acid reflux. ADHD is estimated to affect 4.4 percent of US adults aged 18 to 44 based on results from the National Comorbidity Survey Replication. When this percentage is extrapolated to the full US population aged 18 and over, approximately 9.8 million adults are believed to have ADHD.”

“These study findings may be of particular significance for adults who are taking an ADHD medication along with a proton pump inhibitor, as proton pump inhibitors tend to decrease the production of acid in the stomach,” said Dr. Matthew Brams, a psychiatrist in private practice with Bayou City Research, Ltd. in Houston, TX. “In this study, the conversion of VYVANSE to its active form was not affected when coadministered with Prilosec OTC 40 mg, which relates to the characteristics of VYVANSE as a prodrug stimulant.”

As a prodrug, VYVANSE is converted to its active form by the body’s natural metabolism. This conversion takes place minimally in the gastrointestinal tract and primarily in the blood. Additional pharmacokinetic studies have demonstrated that the conversion of VYVANSE to active medication is unlikely to be affected by alterations in GI transit times and does not rely on gastric pH. ADDERALL XR has a drug delivery system which utilizes immediate release and pH dependent release beads. This pH-dependent delivery system has one type of bead designed to be released immediately and the other type to be released approximately four hours later in the lower intestine where pH levels are higher.

The drug interactions section of the ADDERALL XR product labeling states that coadministration of ADDERALL XR and proton pump inhibitors should be avoided, as these medications act on proton pumps by blocking acid production thereby reducing gastric acidity.

About the Study

This phase I, open-label, randomized, four-period crossover study evaluated the pharmacokinetics of VYVANSE and ADDERALL XR, alone and with Prilosec OTC 40 mg, among 24 healthy adults aged 18 to 45 years. In the study, subjects were administered single oral doses of VYVANSE 50 mg and ADDERALL XR 20 mg at four-day intervals. Following washout, subjects then began a regimen of 40 mg Prilosec OTC once daily for 14 days. Alternate single doses of VYVANSE 50 mg and ADDERALL XR 20 mg were added on days seven and 11.

When ADDERALL XR was administered alone, the median time to maximum plasma amphetamine concentration was five hours. The median time to maximum amphetamine plasma concentration was shortened from five hours to 2.75 hours when ADDERALL XR was coadministered with Prilosec OTC 40 mg. Approximately 57 percent of subjects who received ADDERALL XR with Prilosec OTC had a shortened time to maximum amphetamine plasma concentration of greater than or equal to one hour. When VYVANSE was administered alone, the median time to maximum plasma d-amphetamine concentration was three hours. This remained unchanged when VYVANSE was coadministered with Prilosec OTC. Approximately 25 percent of subjects who received VYVANSE with Prilosec OTC had a shortened time to maximum d-amphetamine plasma concentration of greater than or equal to one hour. The study showed while time to maximum plasma concentration with ADDERALL XR was affected by coadministration with a Prilosec OTC, coadministration with VYVANSE or ADDERALL XR did not affect the maximum plasma concentration or overall exposure to active medication.

Safety was also evaluated during the study. The most common (greater than or equal to 5 percent) treatment emergent adverse events associated with VYVANSE were anxiety, vasospasm, headache, dizziness, palpitations, and tachycardia. The most common (greater than or equal to 5 percent) treatment emergent adverse events associated with ADDERALL XR were vasospasm and anxiety.

VYVANSE, which was introduced in the United States in July 2007 for the treatment of ADHD in children aged 6 to 12 years and approved in April 2008 to treat ADHD in adults, is currently available in six dosage strengths of 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, and 70 mg. To date, more than 5 million VYVANSE prescriptions have been filled, bringing the current US market share to nearly 12 percent based on weekly branded prescription volume. Additionally, VYVANSE formulary coverage has been positive, with 10 of Shire’s top 11 managed care organizations covering the product in a preferred formulary position.

Additional information about VYVANSE and Full Prescribing Information, including the Medication Guide, are available at www.vyvanse.com. Additional information about ADDERALL XR and Full Prescribing Information, including the Medication Guide, are available at www.adderallxr.com.

Note: Prilosec OTC is a registered trademark of Procter & Gamble.

About VYVANSE and ADDERALL XR

Vyvanse is indicated for the treatment of ADHD. Efficacy based on two controlled trials in children aged 6 to 12 and one controlled trial in adults. Adderall XR is indicated for the treatment of ADHD.

Tell the doctor about any heart conditions, including structural abnormalities, that you, your child, or a family member, may have. Inform the doctor immediately if you or your child develops symptoms that suggest heart problems, such as chest pain or fainting.

Vyvanse or Adderall XR should not be taken if you or your child has advanced disease of the blood vessels (arteriosclerosis); symptomatic heart disease; moderate to severe high blood pressure; overactive thyroid gland (hyperthyroidism); known allergy or unusual reactions to drugs called sympathomimetic amines (for example, pseudoephedrine); seizures; glaucoma; a history of problems with alcohol or drugs; agitated states; taken a monoamine oxidase inhibitor (MAOI) within the last 14 days.

Tell the doctor before taking Vyvanse or Adderall XR if you or your child is being treated for or has symptoms of depression (sadness, worthlessness, or hopelessness) or bipolar disorder; has abnormal thought or visions, hears abnormal sounds, or has been diagnosed with psychosis; has had seizures or abnormal EEGs; has or has had high blood pressure; exhibits aggressive behavior or hostility. Tell the doctor immediately if you or your child develops any of these conditions or symptoms while taking Vyvanse or Adderall XR.

Abuse of amphetamines may lead to dependence. Misuse of amphetamine may cause sudden death and serious cardiovascular adverse events. These events have also been reported rarely with amphetamine use.

Talk to your health care provider if your child experiences slowing of growth (height and weight). Children should have their height and weight checked periodically while taking Vyvanse or Adderall XR. Your healthcare provider may stop Vyvanse or Adderall XR treatment if a problem is found during these check-ups.

Vyvanse and Adderall XR were generally well tolerated in clinical studies. The most common side effects reported in studies of Vyvanse were: children – decreased appetite, difficulty falling asleep, stomachache, and irritability; adult – decreased appetite, difficulty falling asleep, and dry mouth. The most common side effects reported in studies of Adderall XR were: children – decreased appetite, difficulty falling asleep, stomachache, and emotional lability; adolescents – loss of appetite, difficulty falling asleep, stomachache, and weight loss; adults – dry mouth, loss of appetite, difficulty falling asleep, headache, and weight loss.

Aggression, new abnormal thoughts/behaviors, mania, growth suppression, worsening of motion or verbal tics, and Tourette’s syndrome have been associated with use of drugs of this type. Tell the doctor if you or your child has blurred vision while taking Vyvanse or Adderall XR.

About ADHD

ADHD is one of the most common psychiatric disorders in children and adolescents. Worldwide prevalence of ADHD is estimated at 5.3 percent (with large variability), according to a comprehensive systematic review of this topic published in 2007 in the American Journal of Psychiatry. In the United States, approximately 7.8 percent of all school-aged children, or about 4.4 million children aged 4 to 17 years, have been diagnosed with ADHD at some point in their lives, according to the US Centers for Disease Control and Prevention (CDC). The disorder is also estimated to affect 4.4 percent of US adults aged 18-44 based on results from the National Comorbidity Survey Replication. When this percentage is extrapolated to the full US population aged 18 and over, approximately 9.8 million adults are believed to have ADHD.

ADHD is a psychiatric behavioral disorder that manifests as a persistent pattern of inattention and/or hyperactivity-impulsivity that is more frequent and severe than is typically observed in individuals at a comparable level of development. The specific etiology of ADHD is unknown and there is no single diagnostic test for this syndrome. Adequate diagnosis requires the use of medical and special psychological, educational and social resources, utilizing diagnostic criteria such as Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) or International Classification of Diseases 10 (ICD-10).

Although there is no “cure” for ADHD, there are accepted treatments that specifically target its symptoms. Standard treatments include educational approaches, psychological, or behavioral modification, and medication.

SHIRE PLC

Shire’s strategic goal is to become the leading specialty biopharmaceutical company that focuses on meeting the needs of the specialist physician. Shire focuses its business on attention deficit hyperactivity disorder (ADHD), human genetic therapies (HGT) and gastrointestinal (GI) diseases as well as opportunities in other therapeutic areas to the extent they arise through acquisitions. Shire’s in-licensing, merger and acquisition efforts are focused on products in specialist markets with strong intellectual property protection and global rights. Shire believes that a carefully selected and balanced portfolio of products with strategically aligned and relatively small-scale sales forces will deliver strong results.

For further information on Shire, please visit the Company’s website: www.shire.com.

THE “SAFE HARBOR” STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995

Statements included herein that are not historical facts are forward-looking statements. Such forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, the Company’s results could be materially adversely affected. The risks and uncertainties include, but are not limited to, risks associated with: the inherent uncertainty of research, development, approval, reimbursement, manufacturing and commercialization of the Company’s Specialty Pharmaceutical and Human Genetic Therapies products, as well as the ability to secure and integrate new products for commercialization and/or development; government regulation of the Company’s products; the Company’s ability to manufacture its products in sufficient quantities to meet demand; the impact of competitive therapies on the Company’s products; the Company’s ability to register, maintain and enforce patents and other intellectual property rights relating to its products; the Company’s ability to obtain and maintain government and other third-party reimbursement for its products; and other risks and uncertainties detailed from time to time in the Company’s filings with the Securities and Exchange Commission.

SOURCE Shire plc


Source: newswire